Stable and Reusable Pd/Cu Bimetallic Nanoparticle Catalysts for the Synthesis of Hydroxy Isoindolones by Domino C‐H Activation and Annulation

A domino C−H activation and annulation process catalyzed by stable and reusable bimetallic nanoparticles (Pd/Cu‐binapthyl nanoparticles) was developed for the synthesis of 3‐hydroxyisoindolin‐1‐ones/thiones. The scope of the reaction was examined utilizing a variety of N ‐alkoxy benzamide/benzothioamide derivatives and benzaldehydes, which yielded moderate to good yields of 3‐hydroxyisoindolin‐1‐ones/thiones, one of which was used to synthesize a BRD4 inhibitor. A gram‐scale synthesis is also reported. The Pd/Cu‐binapthyl nanocatalyst has been recovered and reused up to four times without any major change in particle size and reactivity.